What's Next in TRK-Targeted Therapies

Alexander Drilon, MD: The next steps in terms of developing targeted therapy for patients whose cancers harbor a TRK fusion is obviously looking much more closely at resistance, trying to flesh out the true frequency of both on-target resistance to earlier-generation TRK inhibitors, like larotrectinib and entrectinib, and also off-target resistance. And thereafter, after developing a much more comprehensive understanding of the true frequency of those mechanisms of resistance across cancer types, it’s really diving deeper in developing targeted therapeutics for each of these states.

As I mentioned, there are second-generation, or next-generation, TRK inhibitors that are currently being explored in the clinic. So those are now available for patients. With an increase in the number of patients we put on to those trials, we’ll have a better understanding of the true response rate and durability of next-generation TRK inhibitor use in those patients. But also I think an unmet need is figuring out what happens in cancers that may not be as reliant on the TRK fusion because they have bypass resistance and looking at developing maybe combinatorial therapies for those patients.

But overall, I think the outlook for patients whose cancers harbor a TRK fusion is very good. Even with the first-generation agents we’re seeing very brisk and very durable responses to treatment, and that bodes well if you find this fusion in your patient’s cancer.

Transcript Edited for Clarity

Transcript:

Alexander Drilon, MD: The next steps in terms of developing targeted therapy for patients whose cancers harbor a TRK fusion is obviously looking much more closely at resistance, trying to flesh out the true frequency of both on-target resistance to earlier-generation TRK inhibitors, like larotrectinib and entrectinib, and also off-target resistance. And thereafter, after developing a much more comprehensive understanding of the true frequency of those mechanisms of resistance across cancer types, it’s really diving deeper in developing targeted therapeutics for each of these states.

As I mentioned, there are second-generation, or next-generation, TRK inhibitors that are currently being explored in the clinic. So those are now available for patients. With an increase in the number of patients we put on to those trials, we’ll have a better understanding of the true response rate and durability of next-generation TRK inhibitor use in those patients. But also I think an unmet need is figuring out what happens in cancers that may not be as reliant on the TRK fusion because they have bypass resistance and looking at developing maybe combinatorial therapies for those patients.

But overall, I think the outlook for patients whose cancers harbor a TRK fusion is very good. Even with the first-generation agents we’re seeing very brisk and very durable responses to treatment, and that bodes well if you find this fusion in your patient’s cancer.